Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria.

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole-genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modeled as a mixture of sources from ancient Anatolia, Levant, and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam.

Practical Guidance for Using Behavioral Risk Factor Surveillance System Data: Merging States and Scoring Adverse Childhood Experiences.

Introduction: The Behavioral Risk Factor Surveillance System is a national health-related survey with an optional adverse childhood experience (ACE) module. States use varying methodologies, question formats, and sampling frames, and little guidance exists for conducting multistate explorations of adverse childhood experiences. In this study, 6 adverse childhood experience scoring approaches are compared, and practical recommendations are offered for when and how each approach can be utilized most effectively.

Drivers underpinning the malignant transformation of giant cell tumour of bone.

The rare benign giant cell tumour of bone (GCTB) is defined by an almost unique mutation in the H3.3 family of histone genes H3-3A or H3-3B; however, the same mutation is occasionally found in primary malignant bone tumours which share many features with the benign variant. Moreover, lung metastases can occur despite the absence of malignant histological features in either the primary or metastatic lesions.

Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death.

Expression of the transcription factor brachyury (TBXT) is normally restricted to the embryo, and its silencing is epigenetically regulated. TBXT promotes mesenchymal transition in a subset of common carcinomas, and in chordoma, a rare cancer showing notochordal differentiation, TBXT acts as a putative oncogene. We hypothesized that TBXT expression is controlled through epigenetic inhibition to promote chordoma cell death.

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours.

Diagnosing MPNST can be challenging, but genetic alterations recently identified in polycomb repressive complex 2 (PRC2) core component genes, EED and SUZ12, resulting in global loss of the histone 3 lysine 27 trimethylation (H3K27me3) epigenetic mark, represent drivers of malignancy and a valuable diagnostic tool. However, the reported loss of H3K27me3 expression ranges from 35% to 84%. We show that advances in molecular pathology now allow many MPNST mimics to be classified confidently.

Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma.

The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours.

ZMYM2 inhibits NANOG-mediated reprogramming.

NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some of these were shown to play a role in its ability to mediate reprogramming. In this study, we set out to analyse the effect of NANOG interactors on the reprogramming process.

Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.

The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion only delays and does not prevent transition to formative pluripotency.

Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways.

Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling.

Stem cell function and stress response are controlled by protein synthesis.

Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis.

Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis.

Naive pluripotency is manifest in the preimplantation mammalian embryo. Here we determine transcriptome dynamics of mouse development from the eight-cell stage to postimplantation using lineage-specific RNA sequencing. This method combines high sensitivity and reporter-based fate assignment to acquire the full spectrum of gene expression from discrete embryonic cell types.

The methyl binding domain 3/nucleosome remodelling and deacetylase complex regulates neural cell fate determination and terminal differentiation in the cerebral cortex.

Background: Chromatin-modifying complexes have key roles in regulating various aspects of neural stem cell biology, including self-renewal and neurogenesis. The methyl binding domain 3/nucleosome remodelling and deacetylation (MBD3/NuRD) co-repressor complex facilitates lineage commitment of pluripotent cells in early mouse embryos and is important for stem cell homeostasis in blood and skin, but its function in neurogenesis had not been described. Here, we show for the first time that MBD3/NuRD function is essential for normal neurogenesis in mice.

CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities.

CODEX (http://codex.stemcells.cam.

Impact of exercise training without caloric restriction on inflammation, insulin resistance and visceral fat mass in obese adolescents.

Background: Exercise training has been shown to improve cardiometabolic health in obese adolescents.

Objectives: Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles.

Methods: We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.

Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders.

Mutations in the cytosine-5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities in mice and human. How post-transcriptional methylation contributes to the human disease is currently unknown. By comparing gene expression data with global cytosine-5 RNA methylomes in patient fibroblasts and NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the angiogenin-mediated endonucleolytic cleavage of transfer RNAs (tRNA) leading to an accumulation of 5' tRNA-derived small RNA fragments.

TRES predicts transcription control in embryonic stem cells.

Summary: Unraveling transcriptional circuits controlling embryonic stem cell maintenance and fate has great potential for improving our understanding of normal development as well as disease. To facilitate this, we have developed a novel web tool called 'TRES' that predicts the likely upstream regulators for a given gene list. This is achieved by integrating transcription factor (TF) binding events from 187 ChIP-sequencing and ChIP-on-chip datasets in murine and human embryonic stem (ES) cells with over 1000 mammalian TF sequence motifs.

The epidermis comprises autonomous compartments maintained by distinct stem cell populations.

The complex anatomy of the epidermis contains multiple adult stem cell populations, but the extent to which they functionally overlap during homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we demonstrate that Lrig1(+ve) cells are highly proliferative epidermal stem cells. Long-term clonal analysis reveals that Lrig1(+ve) cells maintain the upper pilosebaceous unit, containing the infundibulum and sebaceous gland as independent compartments, but contribute to neither the hair follicle nor the interfollicular epidermis, which are maintained by distinct stem cell populations.

NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs.

Autosomal-recessive loss of the NSUN2 gene has been identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNAs), yet the identification of cytosine methylation in other RNA species has been hampered by the lack of sensitive and reliable molecular techniques. Here, we describe miCLIP as an additional approach for identifying RNA methylation sites in transcriptomes.

Three carcinomas in one eyelid.

A 90-year-old woman presented with 2 masses on the right lower eyelid. Excisional biopsy revealed 1 lesion to be Merkel cell carcinoma and the other to be invasive squamous cell carcinoma. The patient also had a prior history of basal cell carcinoma in the same eyelid.

Intraocular lens power requirements for humanitarian missions.

Purpose: To develop a generalized method to determine an optimum set of intraocular lens (IOL) powers for humanitarian missions.

Setting: Humanitarian missions to Central America, South America, and Southeast Asia.

Methods: Biometric data of adults who had cataract surgery on 2 humanitarian missions were reviewed, and the ideal emmetropic IOL power for each eye was calculated.

Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs.

Unlabelled: Fever without localising signs in very young children remains a diagnostic problem. Until present, a clinical scoring system combined with leucocyte count, urine analysis and determination of CRP are recognised as being helpful to identify patients at risk of serious bacterial illness. In this study we asked the question whether the determination of procalcitonin (PCT), interleukin (IL)-6, IL-8 and interleukin-1 receptor antagonist (IL- Ra) was superior to these commonly used markers for the prediction of a serious bacterial infection (SBI).

Tumour necrosis factor alpha and its soluble receptors in juvenile chronic arthritis.

Objective: To identify possible imbalance of tumour necrosis factor alpha (TNFalpha) and its soluble receptors in the different subgroups of juvenile chronic arthritis (JCA).

Methods: Serum and synovial fluid samples from 45 children were examined, 25 pauciarticular JCA, 13 polyarticular JCA and seven spondyloarthropathy. TNFalpha, sTNFRI and sTNFRII levels were measured by EASIA and enzyme-linked immunosorbent assay (ELISA).

[Hemorrhagic complications of lower turbinectomy].

Concerning 52 inferior turbinectomies, the authors analyse the haemorrhagic complications of these surgical operations. They deplore 4% of serious haemorrhages. These ones may immediately occur during the surgical operation or in the next 15 days.

The effect of tick infestation on the productivity of cows of three breeds of cattle.

The effect of tick infestation of Hereford, Bonsmara and Nguni cows on the weaning masses of their calves in a dipping versus non-dipping situation was investigated. Breed had a major effect on the level of tick infestation, Herefords being most susceptible and Ngunis least. The productivity of Nguni cows, as measured by the weaning masses of their calves was also least affected.